T-34 tripeptide (Chonluten) Actions on Oxidative Stress and Inflammation

T-34 tripeptide is often referred to by its trade name, Chonluten. Peptide T-34 is a small tripeptide composed of the amino acids glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly)—abbreviated EDG. First described by Khavinson et al., T-34 belongs to a broader class of short peptides proposed to function as potential bioregulators of gene expression. ⁽¹⁾ T-34 in particular appears to be isolated from bronchial epithelial cell cultures.

Due to its diminutive size, researchers in Khavinson’s team, such as Fedoreyeva et al., have suggested that small peptides like T-34 may penetrate cellular membranes more readily than larger proteins, potentially even reaching the nucleus. ⁽²⁾ There, Khavinson et al. posit that such peptides, “consisting of 2-7 amino acid residues, may penetrate the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA.”⁽¹⁾ In vitro studies have begun to explore how T-34 might provide support to pathways governing inflammation and oxidative stress. Below, we will highlight some of the most notable research publications on the topic.

 

Research

T-34 Tripeptide Actions on Oxidative Stress and Tissue Damage Mitigation

Further research by Khavinson et al., specifically focusing on T-34, suggests that this biomodulator may have potential mechanisms related to the modulation of oxidative stress. ⁽³⁾ Specifically, the researchers suggest that the peptide may “mitigate the synthesis of superoxide dismutase (SOD), TNF-α, and Cox-2 mRNA.” This assertion is drawn from research by Avolio et al., who, based on experimental data from their study, suggested that T-34 may exert a “reset” on the tissue’s antioxidant machinery. This is thought to be due to direct modulation of superoxide dismutase (SOD) gene expression. ⁽⁴⁾

In laboratory settings designed to observe the damaged mucosa cells of murine models, SOD mRNA levels have been observed to increase significantly as cells contribute to the neutralization of an overwhelming burden of superoxide radicals. By restoring SOD transcription to its physiological baseline, T-34 is believed to support a more balanced antioxidant environment that is sufficient in SOD to neutralize reactive oxygen species (ROS), but not so excessive that redox signaling and cellular repair pathways are disrupted. This recalibration may result in the controlled clearance of ROS.

This type of clearance is thought to protect lipids, proteins, and DNA from oxidative chain reactions that may otherwise stimulate epithelial injury and delay tissue recovery. Simultaneously, T-34 was suggested to exert actions on the nitric oxide (NO) axis by normalizing both constitutive (cNOS) and inducible (iNOS) nitric oxide synthase expression. In the context of an acute tissue injury, iNOS may become hyperexpressed in response to proinflammatory signals.

In theory, this process may lead to excessive amounts of NO that react with superoxide to form peroxynitrite, a potent oxidant. Meanwhile, dysregulated cNOS may alter vascular tone and microcirculatory flow. By apparently mitigating the implications of both enzymes back toward a normal state, T-34 may limit nitrosative stress and mitigate NO-mediated apoptosis or necrosis of the mucosal cells. ⁽⁴⁾

T-34 Tripeptide Potential For Anti-Inflammatory Modulation

In addition to potentially shielding cells from immediate chemical injury by modulating oxidative stress, the aforementioned research by Avolio et al. suggests that T-34 may mitigate the release of downstream pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), as well as mitigate the levels of adhesion molecules. ⁽⁴⁾ By restoring TNF-α and COX-2 mRNA to those seen in normal mucosa cells, T-34 appears to mitigate the activity of these cytokines and enzyme outputs at their source, curbing local inflammatory signaling before it escalates.

The T-34 tripeptide has also been suggested to lower the overexpressed NF-κB p65 subunit in damaged tissue collected from research models, thereby apparently dampening this major inflammation regulator, which is considered to govern hundreds of downstream pro-inflammatory genes. With NF-κB activity restrained, researchers posit that there is less induction of adhesion molecules such as ICAM-1 (Intercellular Adhesion Molecule-1) and VCAM-1 (Vascular Cell Adhesion Molecule-1), which in turn may mitigate immune cell recruitment and endothelial adhesion, key steps in the amplification of inflammation.

T-34 may also modify stress response proteins, such as lowering HSP70 (heat shock protein 70) levels, which are typically produced by cells in response to cellular stress and may also potentiate inflammatory cascades. Avolio et al. suggested that the peptide may lower HSP70 levels to those seen in normal mucosa cells, indicating a restoration of cellular homeostasis. ⁽⁴⁾ Yet another publication by Khavinson et al. further builds on the peptide’s potential for anti-inflammatory modulation. ⁽⁵⁾ They suggest that even in the absence of the aforementioned pro-inflammatory stimuli, such as tissue damage, T-34 may induce a low‐level TNFα secretion, preconditioning cells toward tolerance rather than full activation and thus inducing a TNF-tolerance state. Then, if these primed monocytes or fully differentiated macrophages do face a strong inflammatory trigger, the T-34-exposed cells appear to release far less TNF-α and interleukin-6 (IL-6), another key inflammatory messenger.

At the heart of these actions may be the STAT proteins—Signal Transducers and Activators of Transcription. Typically, researchers suggest that cytokines may bind to cell-surface receptors, activate JAK enzymes within the cell, and induce STATs to become activated. Activated STATs then move into the nucleus to regulate the expression of specific genes. Khavinson’s team suggests that T-34 may mitigate the activation of STAT3 (which normally drives IL-6 production) while boosting STAT1 activity—even though it may not raise levels of interferon-α (IFN-α), the usual STAT1 trigger. ⁽⁵⁾ These researchers further suggest that phosphorylated STAT1 may build up in the nucleus of T-34-exposed macrophages and may, in turn, shift gene expression toward resolving inflammation.

The T-34 tripeptide may also modulate key kinase pathways, which may activate or deactivate different proteins involved in inflammation, tissue repair, and cellular proliferation. For example, it may increase the activation of ERK1/2 (Extracellular Signal–Regulated Kinases 1 and 2), which are part of the MAPK pathway, suggesting that the peptide may support controlled cell proliferation and tissue repair. JNK (c-Jun N-terminal kinase) is proposed as another member of the MAPK family that activates in response to stress, thereby promoting antioxidant defenses.

The T-34 tripeptide appears to support JNK phosphorylation. This suggests that exposure to the peptide may help cells detoxify harmful byproducts. The experiments by Khavinson et al. also suggest that when monocytes primed with T-34 encounter inflamed blood vessels, these immune cells may stick much less tightly. ⁽⁵⁾ This is posited also to be related to the potential of T-34 to curb the expression of ICAM-1 and VCAM-1 on immune cells and endothelial cells. Fewer “sticky” interactions may mean fewer immune cells are recruited to the vessel wall, possibly dampening the escalation of inflammation.

You can find Chonluten for sale with 99% purity, on our website (available for research use only).

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References:

1. Khavinson, V. K., Popovich, I. G., Linkova, N. S., Mironova, E. S., & Ilina, A. R. (2021). Peptide Regulation of Gene Expression: A Systematic Review. Molecules (Basel, Switzerland), 26(22), 7053. https://doi.org/10.3390/molecules26227053
2. Fedoreyeva, L. I., Kireev, I. I., Khavinson, V. K.h, & Vanyushin, B. F. (2011). Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry. Biokhimiia, 76(11), 1210–1219. https://doi.org/10.1134/S0006297911110022
3. Khavinson, V. K., Lin’kova, N. S., & Tarnovskaya, S. I. (2016). Short Peptides Regulate Gene Expression. Bulletin of experimental biology and medicine, 162(2), 288–292. https://doi.org/10.1007/s10517-016-3596-7
4. Avolio, F., Martinotti, S., Khavinson, V. K., Esposito, J. E., Giambuzzi, G., Marino, A., Mironova, E., Pulcini, R., Robuffo, I., Bologna, G., Simeone, P., Lanuti, P., Guarnieri, S., Trofimova, S., Procopio, A. D., & Toniato, E. (2022). Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. International journal of molecular sciences, 23(7), 3607. https://doi.org/10.3390/ijms23073607
5. Khavinson, V. K.h, Lin’kova, N. S., Dudkov, A. V., Polyakova, V. O., & Kvetnoi, I. M. (2012). Peptidergic regulation of expression of genes encoding antioxidant and anti-inflammatory proteins. Bulletin of experimental biology and medicine, 152(5), 615–618. https://doi.org/10.1007/s10517-012-1590-2